STATISTICAL GENETICS OF PDGF RELATED PHENOTYPES

描述（改编自研究者摘要）：血小板和 血小板产品，如血小板衍生生长因子（PDGF）， 对维持止血至关重要，并持续涉及 在动脉粥样硬化形成中。 然而，人们对遗传学知之甚少。 血小板生物学中正常数量变化的测定。 的 这项研究的总体目标是检测基因的影响， 血小板储存PDGF和其他性状的正常生物学变化 影响其在非人类灵长类动物模型中的可用性和活性 治疗动脉粥样硬化 统计遗传学方法将用于检测 并测量未知的主要基因座，已知的 候选基因座、匿名微卫星基因座和多基因 血小板储存的PDGF和其他PDGF相关的定量变化 性状 这些性状，包括血小板数量和体积，血清 血小板活化因子（PAF）、血浆血栓素B2、血清胰岛素- 类生长因子-1（IGF-1）、总脂蛋白和高密度脂蛋白 将在600只纯种狒狒中测量胆固醇。 每只动物的 在6个多态性候选位点上的基因型-包括PDGF-B链和 IGF-1基因座，以及PDGF-B、IGF-1、血栓素A2和PAF基因座 受体-将通过聚合酶链反应方法测定。 最大似然定量遗传和复杂分离分析 将用于估计遗传力，主基因的影响， 多基因、主效基因和候选基因的联合效应 这些特征的多态性。 复偏析分析的扩展 将用于检测基因型的差异表达， 协变量，例如，性别和年龄 基于形式变换参数的 LOD评分分析和稳健方差分量分析将用于 用候选位点和匿名者检测数量性状连锁 目前正在开发的狒狒基因组图谱的微卫星标记 同样的动物。 拟议的项目将增加我们的知识 关于PDGF正常数量变异的遗传决定因素 和相关的表型，提供有关的程度和性质， 这些表型之间的协变有助于定位基因组区域， 负责这些性状的变化，并进一步建立 纯种狒狒作为动脉粥样硬化相关遗传研究的模型。

DESCRIPTION (Adapted from the Investigator's Abstract): Platelets and platelet products, like platelet-derived growth factor (PDGF), are critical to the maintenance of hemostasis and are continually implicated in atherogenesis. However, little is understood about the genetic determination of normal quantitative variation in platelet biology. The overall objective of the proposed study is to detect the effects of genes on normal biological variation in platelet-stores of PDGF and other traits which influence its availability and activity in a nonhuman primate model for atherosclerosis. Statistical genetic methods will be used to detect and measure the effects of variation at unknown major loci, known candidate loci, anonymous microsatellite loci, and polygenes on quantitative variation in platelet stored PDGF and other PDGF-related traits. These traits, including platelet number and volume, serum platelet activating factor (PAF), plasma thromboxane B2, serum insulin- like growth factor-1 (IGF-1), and total and high density lipoprotein cholesterol, will be measured in 600 pedigreed baboons. Each animal's genotype at 6 polymorphic candidate loci -- including PDGF-B chain and IGF- loci, and the loci for the PDGF-B, IGF-1, thromboxane A2, and PAF receptors -- will be determined by polymerase chain reaction methods. Maximum-likelihood quantitative genetic and complex segregation analyses will be used to estimate heritabilities, the effects of major genes, and the joint effects of polygenes, major loci, and candidate gene polymorphisms on these traits. Extensions of complex segregation analysis will be used to detect differential expression of genotypes as functions of covariates, e.g., sex and age. Both formal penetrance-parameter-based LOD score analysis and robust variance components analysis will be used to detect quantitative trait linkage with candidate loci and the anonymous microsatellite markers from a baboon genome map currently being developed for the same animals. The proposed project will increase our knowledge about the genetic determinants of normal quantitative variation in PDGF and related phenotypes, provide information on the extent and nature of covariation among these phenotypes, help localize genomic regions responsible for variation in these traits, and further establish the pedigreed baboon as a model for atherosclerosis-related genetic research.